As a method for detecting a substance distribution on a measurement object surface particularly in the field of pathology research and drug development, “imaging mass spectrometry” has recently been attracting attention. The imaging mass spectrometry is a method of obtaining distribution information of a substance on a surface of a measurement object by performing two-dimensional mass spectrometry of the surface of the measurement object and obtaining a two-dimensional distribution of detected intensity of the substance corresponding to a mass-to-charge ratio. With the imaging mass spectrometry, it is possible to identify a biological molecule such as protein, a drug molecule, and the like and to measure a spatial distribution of the molecule with high spatial resolution.
A mass spectrometry, in general, is a method of ionizing a sample by irradiating the sample with laser light, an ion, an electron, or the like and separating the ionized sample by the mass-to-charge ratio, to thereby obtain a spectrum formed of a mass-to-charge ratio and detected intensity thereof.
As a unit for generating an ion from a measurement object, charged particle beams such as a laser beam and an ion beam (hereinafter collectively referred to as a primary beam) are usable. In the case where the primary beam is the ion beam, the emitted ion is called a secondary ion. As examples of using the laser as the primary beam, a matrix-aided laser desorption ionization (MALDI) for attaining the ionization by irradiating a sample, which being blended with a matrix and crystallized, with pulsed and finely focused laser light, and secondary ion mass spectrometry (SIMS) for attaining ionization by irradiating a sample with a primary ion beam, have been known.
As a method for separating the ionized sample by a mass-to-charge ratio and detecting the sample, a time-of-flight type which is suitable for detecting a molecule having a large mass, such as a protein, is often adopted to the imaging mass spectrometry. In a time-of-flight mass spectrometer, an ion is emitted from a surface of a measurement object in a pulsed manner, and the ion is accelerated in vacuum by an electric field. Since flight speeds of ions are each different depending on its mass-to-charge ratio, the mass-to-charge ratio of the target ion can be measured by measuring a time required for the target ion to fly a certain distance from the measurement object to a detection device.
Also, the imaging mass spectrometry includes two methods, namely, a scanning type and a projection type.
The scanning type is a method including sequentially performing mass spectrometry of fine areas (depends on a beam diameter of a primary beam) on a measurement object and re-constructing a distribution of a substance from results of the mass spectrometry and position information of the fine areas.
In the projection type, a measurement object of a wide area is ionized by irradiating an entire surface of the measurement object with a primary beam having a relatively wide irradiation area, and a time required for a generated ion to arrive at a detection device and a position of arrival of the ion on a surface of the detection device are measured by a position/time sensitive detector. With such configuration, it is possible to measure a spatial distribution of a substance contained in the measurement object by simultaneously detecting a mass of the detected ion and a position of the ion on the surface of the measurement object.
As a representative mass spectrometer, the one using laser light as the primary beam (PTL 1) and the one using an ion beam (PTL 2) have been disclosed.